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International Journal of Vascular Medicine
Volume 2012, Article ID 246058, 9 pages
Research Article

Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan

Received 12 April 2012; Revised 21 May 2012; Accepted 8 June 2012

Academic Editor: Rei Shibata

Copyright © 2012 Yasuhiro Izumiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 μg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production.